Compositions comprising particulate material dispersed throughout a liquid carrier suitable for administration to a subject (e.g. animal or human) have long been used in the field of medicine. For example, certain pharmaceutical agents may be provided in the form of an administrable composition in which the agent is dispersed or suspended throughout a liquid carrier. Contrast agents for imaging techniques are also typically provided in the form of an administrable composition in which the agent is dispersed or suspended throughout a liquid carrier.
In such compositions it is generally important that the dispersion remains stable (i.e. that the particulate material remains dispersed throughout the carrier liquid) at the very least up until the composition is to be administered. For example, a poorly formulated pharmaceutical dispersion might allow the pharmaceutical agent to settle out from the liquid carrier as sediment, thereby reducing the therapeutic concentration of the agent in the dispersion. This of course could result in under-dosing or over-dosing a patient, which may seriously compromise the patient's treatment.
The importance of the particulate material remaining in a dispersed state might also extend to after the composition has been administered to a subject. For example, it is particularly important that parenterally administered contrast agents remain in a dispersed state in vivo. In particular, flocculation of the contrast agent in vivo can be life-threatening to the subject.
Stabilisers are commonly employed to help maintain the particulate material in a dispersed state. The stabilisers typically function by (a) interacting with both the particulate material and the surrounding liquid environment (i.e. the liquid carrier of the composition or the liquid carrier in vivo), and (b) presenting electrostatic and/or steric repulsion forces that help maintain the particulate material in a dispersed state. A variety of such stabilisers of both natural and synthetic origin are known.
However, under certain circumstances it can be difficult to maintain particulate material in a dispersed state throughout a liquid carrier. For example, it is sometimes desirable or necessary to prepare administrable compositions comprising a liquid carrier having a relatively high ionic strength (e.g. an ionic strength comparable with that in vivo—isotonic). In that case, some stabilisers are simply ineffective in or perform poorly at providing a stable dispersion of the particulate material throughout the liquid carrier. This problem can also present itself post administration of the composition. In particular, liquid carriers presented to the particulate material in vivo can also have a relatively high ionic strength.
In addition to or separate from the effect a given liquid environment may have on a stabilisers ability to maintain the particulate material in a dispersed state, the concentration of the particulate material per se in the liquid environment can also impact on this ability. In particular, those skilled in the art will appreciate that there is typically an equilibrium set up between the interaction of conventional stabilisers with the particulate material and the surrounding liquid environment. Thus, as the volume of the surrounding liquid environment increases relative to a given stabilised particulate material, the equilibrium may shift in favour of the stabiliser spending more time associated with the liquid environment, thereby presenting greater opportunity for the particulate material to flocculate or simply fall out of dispersion. Although this equilibrium is reversed as the volume of surrounding liquid is reduced relative to a given stabilised particulate material (i.e. increased concentration of the particulate material in the surrounding liquid), many stabilisers nevertheless can not maintain particulate material in a dispersed and readily flowable state at concentrations above a modest 40 wt. %.
Such concentration effects can apply to the composition per se prior to its administration and/or to the composition once it has been administered. Those skilled in the art will appreciate that the dilution effect of administering a composition to a subject can be particularly problematic with regard to maintaining particulate material in a stabilised state in vivo for any practical length of time.
An opportunity therefore remains to address or ameliorate one or more disadvantages or shortcomings associated with existing administrable compositions, or to at least provide a useful alternative to conventional administrable compositions.